Methyl 2-(benzhydrylamino)-2-[3-(benzylsulfamoyl)phenyl]acetate | 213488-03-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Methyl 2-(benzhydrylamino)-2-[3-(benzylsulfamoyl)phenyl]acetate
• CAS: 213488-03-0
• 化学式: C₂₉H₂₈N₂O₄S
• 分子量: 500.618
• InChiKey: CJIFOPNDUUZJSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Methyl 2-(benzhydrylamino)-2-[3-(benzylsulfamoyl)phenyl]acetate 在 sodium tetrahydroborate 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 以96%的产率得到3-[1-(benzhydrylamino)-2-hydroxyethyl]-N-benzylbenzenesulfonamide
  参考文献：
  名称：

  β-Amino-thiols Inhibit the Zinc Metallopeptidase Activity of Tetanus Toxin Light Chain

  摘要：

  Tetanus neurotoxin is a 150-kDa protein produced by Clostridium tetani, which causes the lethal spastic paralytic syndromes of tetanus by blocking inhibitory neurotransmitter release at central synapses. The toxin light chain (50 kDa) has a zinc endopeptidase activity specific for synaptobrevin, an essential component of the neuroexocytosis apparatus. Previous unsuccessful attempts to block the proteolytic activity of this neurotoxin with well-known inhibitors of other zinc proteases led us to study the design of specific inhibitors as a possible drug therapy to prevent the progressive evolution of tetanus following infection. Starting from the synaptobrevin sequence at the level of the cleavage site by tetanus neurotoxin (Gln(76)-Phe(77)), a thiol analogue of glutamine demonstrated inhibitory activities in the millimolar range. A structure-activity relationship performed with this compound led us to determine the requirement for the correct positioning of the thiol group, the primary amino group, and a carboxamide or sulfonamide group on the side chain. This resulted in the design of a beta-amino-(4-sulfamoylphenyl)glycine-thiol, the first significantly efficient inhibitor of tetanus neurotoxin with a K-i value of 35 +/- 5 mu M.

  DOI：

  10.1021/jm981015z
• 作为产物：
  描述：

  N-benzyl-3-formylbenzenesulfonamide 在 盐酸 、 甲醇 、 Amberlite IR-120 acidic resin 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 48.0h， 生成 Methyl 2-(benzhydrylamino)-2-[3-(benzylsulfamoyl)phenyl]acetate
  参考文献：
  名称：

  β-Amino-thiols Inhibit the Zinc Metallopeptidase Activity of Tetanus Toxin Light Chain

  摘要：

  Tetanus neurotoxin is a 150-kDa protein produced by Clostridium tetani, which causes the lethal spastic paralytic syndromes of tetanus by blocking inhibitory neurotransmitter release at central synapses. The toxin light chain (50 kDa) has a zinc endopeptidase activity specific for synaptobrevin, an essential component of the neuroexocytosis apparatus. Previous unsuccessful attempts to block the proteolytic activity of this neurotoxin with well-known inhibitors of other zinc proteases led us to study the design of specific inhibitors as a possible drug therapy to prevent the progressive evolution of tetanus following infection. Starting from the synaptobrevin sequence at the level of the cleavage site by tetanus neurotoxin (Gln(76)-Phe(77)), a thiol analogue of glutamine demonstrated inhibitory activities in the millimolar range. A structure-activity relationship performed with this compound led us to determine the requirement for the correct positioning of the thiol group, the primary amino group, and a carboxamide or sulfonamide group on the side chain. This resulted in the design of a beta-amino-(4-sulfamoylphenyl)glycine-thiol, the first significantly efficient inhibitor of tetanus neurotoxin with a K-i value of 35 +/- 5 mu M.

  DOI：

  10.1021/jm981015z

文献信息

• β-Amino-thiols Inhibit the Zinc Metallopeptidase Activity of Tetanus Toxin Light Chain
  作者：Loïc Martin、Fabrice Cornille、Pascale Coric、Bernard P. Roques、Marie-Claude Fournié-Zaluski

  DOI：10.1021/jm981015z

  日期：1998.8.1

  Tetanus neurotoxin is a 150-kDa protein produced by Clostridium tetani, which causes the lethal spastic paralytic syndromes of tetanus by blocking inhibitory neurotransmitter release at central synapses. The toxin light chain (50 kDa) has a zinc endopeptidase activity specific for synaptobrevin, an essential component of the neuroexocytosis apparatus. Previous unsuccessful attempts to block the proteolytic activity of this neurotoxin with well-known inhibitors of other zinc proteases led us to study the design of specific inhibitors as a possible drug therapy to prevent the progressive evolution of tetanus following infection. Starting from the synaptobrevin sequence at the level of the cleavage site by tetanus neurotoxin (Gln(76)-Phe(77)), a thiol analogue of glutamine demonstrated inhibitory activities in the millimolar range. A structure-activity relationship performed with this compound led us to determine the requirement for the correct positioning of the thiol group, the primary amino group, and a carboxamide or sulfonamide group on the side chain. This resulted in the design of a beta-amino-(4-sulfamoylphenyl)glycine-thiol, the first significantly efficient inhibitor of tetanus neurotoxin with a K-i value of 35 +/- 5 mu M.